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羽扇豆醇通过下调 Toll 样受体 4 减轻柯萨奇病毒 B3 诱导的小鼠病毒性心肌炎。

Lupeol alleviates coxsackievirus B3-induced viral myocarditis in mice via downregulating toll-like receptor 4.

机构信息

Department of Cardiac Surgery, Wuhan Asia Heart Hospital, Wuhan, P.R. China *Ming Xu and Xiaoyong Li are co-first authors.

出版信息

J Int Med Res. 2020 Apr;48(4):300060520910908. doi: 10.1177/0300060520910908.

Abstract

OBJECTIVES

To investigate the effect of lupeol in a mouse model of viral myocarditis induced by coxsackie virus B3 (CVB3).

METHODS

Mice were separated into controls (DMEM,  = 20) and CVB3 infected groups (i.e., untreated CVB3 [ = 40]; CVB3 + lupeol 50 mg/kg [ = 40]; CVB3 + lupeol 100 mg/kg [ = 40]; CVB3 + small interfering RNA (siRNA)- toll-like receptor 4 (TLR4) [n = 20]; siRNA + EXP-H mice [n = 20]). Reverse transcription polymerase chain reaction (RT-PCR), western-blot assay, immunohistochemistry, enzyme-linked immunosorbent (ELISA) assay and histopathology were performed to investigate the cardioprotective role of lupeol.

RESULTS

The elevated pro-inflammatory cytokines in CVB3-infected mice (i.e., interleukin-1β [IL-1β]; interleukin-6 [IL-6]; tumour necrosis factor-α [TNF-α]) were significantly reduced by lupeol 50 or 100 mg/kg. Interestingly, the mRNA level and protein level of toll-like receptor 4 (TLR4) were inhibited by lupeol.

CONCLUSIONS

Lupeol alleviates CVB3-induced viral myocarditis and myocardial damage in mice. The underlying mechanism may due to downregulation of TLR4.

摘要

目的

研究羽扇豆醇在柯萨奇病毒 B3(CVB3)诱导的病毒性心肌炎小鼠模型中的作用。

方法

将小鼠分为对照组(DMEM,n=20)和 CVB3 感染组(即未处理的 CVB3 [n=40];CVB3+羽扇豆醇 50mg/kg [n=40];CVB3+羽扇豆醇 100mg/kg [n=40];CVB3+小干扰 RNA(siRNA)- Toll 样受体 4(TLR4)[n=20];siRNA+EXP-H 小鼠 [n=20])。采用逆转录聚合酶链反应(RT-PCR)、Western blot 分析、免疫组织化学、酶联免疫吸附(ELISA)测定和组织病理学方法研究羽扇豆醇的心脏保护作用。

结果

羽扇豆醇可显著降低 CVB3 感染小鼠升高的促炎细胞因子(即白细胞介素-1β[IL-1β];白细胞介素-6[IL-6];肿瘤坏死因子-α[TNF-α])。有趣的是,羽扇豆醇可抑制 TLR4 的 mRNA 水平和蛋白水平。

结论

羽扇豆醇可减轻 CVB3 诱导的病毒性心肌炎和小鼠心肌损伤。其潜在机制可能与 TLR4 的下调有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9121/7158257/0e5be333872d/10.1177_0300060520910908-fig1.jpg

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